Motor unit integrity in multifocal motor neuropathy: A systematic evaluation with CMAP scans

Abstract

Introduction/aims: Progressive axonal loss in multifocal motor neuropathy (MMN) is often assessed with nerve conduction studies (NCS), by recording maximum compound muscle action potentials (CMAPs). However, reinnervation maintains the CMAP amplitude until a significant portion of the motor unit (MU) pool is lost. Therefore, we performed more informative CMAP scans to study MU characteristics in a large cohort of patients with MMN.

Methods: We derived the maximum CMAP amplitude (CMAP_max ), an MU number estimate (MUNE), and the largest MU amplitude stimulus current required to elicit 5%, 50%, and 95% of CMAP_max (S5, S50, S95) and relative ranges ([S95 - S5] × 100 / S50) from the scans. These metrics were compared with clinical, laboratory, and NCS results.

Results: Forty MMN patients and 24 healthy controls were included in the study. CMAP_max and MUNE were reduced in MMN patients (both P < .001). Largest MU amplitude as a percentage of CMAP_max was increased in MMN patients (P < .001). Disease duration and treatment duration were not associated with MUNE. Relative range was larger in patients with anti-GM1 antibodies than in those without anti-GM1 antibodies (P = .016) and controls (P < .001). The largest MU amplitudes were larger in patients without anti-GM1 antibodies than in patients with anti-GM1 antibodies (P = .037) and controls (P = .044).

Discussion: We found that MU loss is common in MMN and accompanied by enlarged MUs. Presence of anti-GM1 antibodies was associated with increased relative range of MU thresholds and reduction in largest MU amplitude. Our findings indicate that CMAP scans complement routine NCS, and may have potential for practical monitoring of treatment efficacy and disease progression.

Keywords: CMAP scan; anti-ganglioside antibodies; motor unit integrity; motor unit number estimation; multifocal motor neuropathy.

FIGURE 1

CMAP scans of patients with comparable strength scores (MRC = 3), showing wide variability in motor unit number estimates (MUNEs), illustrated by decreasing MUNE values from A‐G. Features of demyelinative slowing were present in A‐C and G‐I. Conduction block (CB) was not observed. NCS variables are depicted at the top left of each scan. Note the intersubject differences in maximum CMAP amplitude (y axis) and stimulus intensities (x axis). Abbreviations: DML, distal motor latency; MCV, motor conduction velocity; red., reduction; dur. prol., duration prolongation

FIGURE 2

A, Boxplot showing motor unit number estimates (MUNEs). B, Boxplot showing largest motor unit amplitude as percentage of maximum CMAP of 39 MMN patients and 24 controls. Solid line: median value; box edges: 25th and 75th percentiles; whiskers: entire range except for outliers. ^***Significant difference (P < .001)

FIGURE 3

Association of strength scores with motor unit number estimates (MUNEs). Restricted cubic splines (solid lines) and 95% confidence intervals (gray areas) depicting (A) the relation between MRC scores and MUNE and (B) the relation between vigorimeter scores and MUNE

FIGURE 4

Motor unit characteristics in patients stratified by presence of anti‐GM1 antibodies and compared with controls. A, Boxplot showing motor unit number estimates (MUNEs). B, Boxplot showing relation between maximum CMAP amplitude and MUNE of patients with (circles and solid line) and without (triangles and dashed line) anti‐GM1 antibodies, and controls (squares and dashed dotted line), with rho indicating Spearman rank coefficient. C. Boxplot showing relative range. D, Boxplot showing largest motor unit amplitude. Solid line: median value; box edges: 25th and 75th percentiles; whiskers: entire range except outliers. Significant differences: *P < .05, **P < .01, and ***P < .001